Lenalidomide for Granulomatous Slack Skin

Granulomatous slack skin is a clinically stable disease, but the only known risk factor is having a sibling with the disease. Its pathophysiology, however, is not fully known, and this disease may not be a unique disease entity.

Granulomatous slack skin is the term for a newly established classification of sarcoid lesions and is distinguished by its characteristic nonaggressive histopathology, benign clinical course, and a lack of immunosuppressive treatments in patients with systemic involvement. Other terms often used for this disease are granuloma-slack sarcoma syndrome and granulomatous sarcoidosis. It can be seen in patients of all ages and in Caucasians, East Africans, Asians, and Hispanics. There is growing interest in granulomatous slack skin and other sarcoid conditions worldwide since sarcoidosis cases have become more prevalent with time.

Granulomatous slack skin is an infrequent, chronic dermatosis with a wide variety of clinical and histopathologic findings. The classic form of granulomatous slack skin consists of non-scarring, non-inflammatory, erythematous papules, typically with a roughened texture. Small nodules, vesiculobullous scars, or fibrosis are also found. Granulomatous slack skin may also present with more severe, non-scarring, inflammatory lesions, such as erythema nodosum, which has a smoother, non-roughened appearance.

Granulomatous slack skin affects 0.6 to 1.0% of people in the US. The prevalence among adults was about 12.3 per 100,000. These values will be higher among the elderly and people of African descent. Granulomatous slack skin is more common in men than in women.

The main treatments include excision, antibiotics (tetracyclines and sulfa- or tetracyclines plus sulfamethoxazole), and/or antimycotic agents including itraconazole, terbinafine, fluconazole, clotrimazole, micafungin, and/or ketoconazole. Anti-fungal immunotherapy may be used for the prevention of recurrence in some cases of granulomatous skin disease. A Cochrane review from 2011 summarised the evidence and reported that no trials provided sufficient information to permit a meta-analysis.

Although a full explanation is not available, we suggest that granulomatous slack skin should not be corrected and should be left to the natural progression of disease. Our observations challenge the conventional paradigm of dermatitis herpetiformis, as well as the notion that granulomatous slack skin can be cured through surgical correction and that this is particularly viable when used to treat refractory disease.

Oral lenalidomide with other treatments was used in an unusually high proportion of patients undergoing treatment, particularly in those who received chemotherapy. In clinical trials, lenalidomide was also used as monotherapy for MDS or PMFL.

People taking lenalidomide in combination with interferon alpha are at increased risk of developing grade 3 and 4 neutropenia. Grade 3 and 4 neutropenia has not previously been described, with grade 4 neutropenia appearing to be a greater problem. It is possible that people taking lenalidomide may also experience an increased risk of infections.

These data support a significant risk in subjects with granulomatous slack skin and suggest that the condition is related to a deficiency in the production of interferon.

Currently there are few studies that report on the efficacy using lenalidomide, thus it is difficult to determine the effectiveness and safety. To find more current evidence, trials in the use of lenalidomide in various conditions will need to be conducted.

The rate of progression of GS skin disease varies greatly depending on the nature of the disease and the patient and can be variable, but generally is around 5 years, or, in an average case, 12 years. The risk of progression seems related to patient demographics and disease progression. Further studies need to be done to determine the factors that may predict the timing of progression.